title: Quercetin inhibits radiation-induced skin fibrosis.
abstract: Radiation induced fibrosis of the skin is a late toxicity that may result in loss of function due to reduced range of motion and pain. The current study sought to determine if oral delivery of quercetin mitigates radiation-induced cutaneous injury. Female C3H/HeN mice were fed control chow or quercetin-formulated chow (1% by weight). The right hind leg was exposed to 35 Gy of X rays and the mice were followed serially to assess acute toxicity and hind leg extension. Tissue samples were collected for assessment of soluble collagen and tissue cytokines. Human and murine fibroblasts were subjected to clonogenic assays to determine the effects of quercetin on radiation response. Contractility of fibroblasts was assessed with a collagen contraction assay in the presence or absence of quercetin and transforming growth factor-β (TGF-β). Western blotting of proteins involved in fibroblast contractility and TGF-β signaling were performed. Quercetin treatment significantly reduced hind limb contracture, collagen accumulation and expression of TGF-β in irradiated skin. Quercetin had no effect on the radioresponse of fibroblasts or murine tumors, but was capable of reducing the contractility of fibroblasts in response to TGF-β, an effect that correlated with partial stabilization of phosphorylated cofilin. Quercetin is capable of mitigating radiation induced skin fibrosis and should be further explored as a therapy for radiation fibrosis.
authors.affiliation: Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Horton
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Chung
authors.forename: Kathryn
authors.initials: K
authors.lastname: Hudak
authors.forename: Ayla
authors.initials: A
authors.lastname: White
authors.forename: Kristopher
authors.initials: K
authors.lastname: Krausz
authors.forename: Frank
authors.initials: F
authors.lastname: Gonzalez
authors.forename: Deborah
authors.initials: D
authors.lastname: Citrin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001711:Biotransformation; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy; D048430:Cell Shape; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D003114:Colony-Forming Units Assay; D004353:Drug Evaluation, Preclinical; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005355:Fibrosis; D017930:Genes, Reporter; D006614:Hindlimb / Q000528:radiation effects; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D041681:NIH 3T3 Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008517:Phytotherapy; D011794:Quercetin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011855:Radiodermatitis / Q000209:etiology / Q000517:prevention & control*; D011878:Radiotherapy / Q000009:adverse effects; D011897:Random Allocation; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000532:radiotherapy; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000975:Antioxidants; D011837:Radiation-Protective Agents; D016212:Transforming Growth Factor beta; D003094:Collagen; D011794:Quercetin